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1.
FASEB J ; 38(3): e23432, 2024 02 15.
Article in English | MEDLINE | ID: mdl-38300173

ABSTRACT

The IGF signaling pathway plays critical role in regulating skeletal myogenesis. We have demonstrated that KIF5B, the heavy chain of kinesin-1 motor, promotes myoblast differentiation through regulating IGF-p38MAPK activation. However, the roles of the kinesin light chain (Klc) in IGF pathway and myoblast differentiation remain elusive. In this study, we found that Klc1 was upregulated during muscle regeneration and downregulated in senescence mouse muscles and dystrophic muscles from mdx (X-linked muscular dystrophic) mice. Gain- and loss-of-function experiments further displayed that Klc1 promotes AKT-mTOR activity and positively regulates myogenic differentiation. We further identified that the expression levels of IRS1, the critical node of IGF-1 signaling, are downregulated in Klc1-depleted myoblasts. Coimmunoprecipitation study revealed that IRS1 interacted with the 88-154 amino acid sequence of Klc1 via its PTB domain. Notably, the reduced Klc1 levels were found in senescence and osteoporosis skeletal muscle samples from both mice and human. Taken together, our findings suggested a crucial role of Klc1 in the regulation of IGF-AKT pathway during myogenesis through stabilizing IRS1, which might ultimately influence the development of muscle-related disorders.


Subject(s)
Insulin-Like Growth Factor I , Proto-Oncogene Proteins c-akt , Animals , Humans , Mice , Insulin Receptor Substrate Proteins/genetics , Kinesins/genetics , Mice, Inbred mdx , Myoblasts , Signal Transduction
2.
Acta Pharmacol Sin ; 44(2): 446-453, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35896694

ABSTRACT

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.


Subject(s)
Biosimilar Pharmaceuticals , Bone Density Conservation Agents , Osteoporosis, Postmenopausal , Osteoporosis , Female , Humans , Biosimilar Pharmaceuticals/adverse effects , Bone Density , Bone Density Conservation Agents/therapeutic use , Bone Remodeling , Denosumab/therapeutic use , Denosumab/pharmacology , Double-Blind Method , East Asian People , Osteoporosis/drug therapy , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/drug therapy , Postmenopause
3.
J Nanobiotechnology ; 21(1): 177, 2023 Jun 03.
Article in English | MEDLINE | ID: mdl-37268942

ABSTRACT

Long-term chronic inflammation after Achilles tendon injury is critical for tendinopathy. Platelet-rich plasma (PRP) injection, which is a common method for treating tendinopathy, has positive effects on tendon repair. In addition, tendon-derived stem cells (TDSCs), which are stem cells located in tendons, play a major role in maintaining tissue homeostasis and postinjury repair. In this study, injectable gelatine methacryloyl (GelMA) microparticles containing PRP laden with TDSCs (PRP-TDSC-GM) were prepared by a projection-based 3D bioprinting technique. Our results showed that PRP-TDSC-GM could promote tendon differentiation in TDSCs and reduce the inflammatory response by downregulating the PI3K-AKT pathway, thus promoting the structural and functional repair of tendons in vivo.


Subject(s)
Platelet-Rich Plasma , Tendinopathy , Rats , Animals , Hydrogels/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Tendons , Tendinopathy/therapy , Tendinopathy/metabolism , Stem Cells , Platelet-Rich Plasma/metabolism , Printing, Three-Dimensional
4.
Int Orthop ; 47(6): 1423-1431, 2023 06.
Article in English | MEDLINE | ID: mdl-37042970

ABSTRACT

PURPOSE: Periprosthetic joint infection (PJI) is a serious hip and knee arthroplasty complication. Despite the increased incidence of primary joint replacements, there is no clear guideline for treating PJI in the Chinese mainland yet. We aim to measure the current situation and basis for surgical treatment methods of PJI in major orthopaedic hospitals in the Chinese mainland. METHODS: We conducted a national survey on PJI treatment in Mainland China. Forty-one top arthroplasty centers were included, with 82.9% (34/41) response rate. The data were analyzed using Microsoft Excel version 20.0 and described as numbers and percentages. RESULTS: For acute infections, prosthesis-preserving procedures (DAIR) are used in all centres. For hip and knee PJI, 20.5% (7/34) and 35% (12/34) of the centres used a one-stage exchange. If applied, this treatment will necessitate the previous patients' selection for a satisfactory outcome. All centres execute the two-stage exchange. Between phases, the majority of centres implant a cemented spacer. Revisions for infected hips included 21 (4.3%) cases of DAIR, 95 (19.9%) cases of single-stage exchange, 362 (75.2%) cases of two-stage exchange, and 2 (0.007%) cases of hip dissection. Revisions for infected knee comprised 88 (19.0%) cases of DAIR, 48 (10.3%) cases of single-stage exchange, 324 (69.8%) cases of two-stage exchange, and 5 (0.02%) cases of knee fusion. CONCLUSIONS: The centers do not have a uniform PJI standard. Most patients have two-stage revision with a cemented spacer in China. These concepts can help establish treatment guidelines.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Prosthesis-Related Infections , Humans , Anti-Bacterial Agents/therapeutic use , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , East Asian People , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/etiology , Prosthesis-Related Infections/surgery , Reoperation , Retrospective Studies , Treatment Outcome , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods
5.
Arthroscopy ; 38(10): 2852-2860, 2022 10.
Article in English | MEDLINE | ID: mdl-35550417

ABSTRACT

PURPOSE: To investigate whether anterior tibial subluxation obtained from magnetic resonance imaging (MRI) could be a predictor of high-grade rotatory instability for anterior cruciate ligament (ACL) injuries, including acute and chronic cases. METHODS: From September 2016 to August 2018, we retrospectively investigated 163 patients with ACL injuries who subsequently underwent primary ACL reconstruction. Among them, 30 patients with high-grade rotatory instability (grade II/III pivot shift) were included in the high-grade group, and their age and sex were matched 1:2 to low-grade cases (3 months) phases. RESULTS: The high-grade group had a larger anterior tibial subluxation of lateral compartment (8.1 mm vs 5.9 mm; P =.004) than the low-grade group, whereas no significant difference was found in anterior tibial subluxation of medial compartment (P > .05). Moreover, high-grade anterior tibial subluxation of lateral compartment (≥6 mm) was found to be an independent predictor (odds ratio, 12.992; P = .011) associated with concomitant meniscal tears after ACL injuries. Anterior tibial subluxation of lateral compartment demonstrated statistical significance between the two groups when comparing subgroups within 3 months but not beyond 3 months. CONCLUSION: In ACL-injured patients, high-grade anterior tibial subluxation of lateral compartment (≥6 mm) could be a unique predictor of high-grade knee rotatory instability for acute but not chronic injuries. Prolonged time from injury to surgery and lateral meniscus tears were risk factors for high-grade rotatory laxity in chronic patients. LEVEL OF EVIDENCE: Level III, retrospective prognostic trial.


Subject(s)
Anterior Cruciate Ligament Injuries , Joint Dislocations , Joint Instability , Anterior Cruciate Ligament Injuries/complications , Anterior Cruciate Ligament Injuries/diagnostic imaging , Anterior Cruciate Ligament Injuries/surgery , Case-Control Studies , Female , Humans , Joint Dislocations/surgery , Joint Instability/complications , Joint Instability/etiology , Knee Joint/surgery , Magnetic Resonance Imaging , Male , Retrospective Studies
6.
Rheumatology (Oxford) ; 60(5): 2383-2390, 2021 05 14.
Article in English | MEDLINE | ID: mdl-33167034

ABSTRACT

OBJECTIVES: OA is the most common form of arthritis worldwide and has a major impact on the quality of life among the older population. This study aimed at determining the potential causal effects of several serum nutritional factors on OA. METHODS: A total of seven serum nutritional factors were identified from genome-wide association studies. Summary statistics for OA were obtained from UK Biobank (194 153 for women and 166 988 for men) and a large genome-wide association studies meta-analysis based on the European population (455 221, 393 873 and 403 124 for overall, hip and knee OA, respectively). Two-sample Mendelian randomization approach was used to estimate the causal association between the selected nutritional factors and the risk of OA. RESULTS: The Mendelian randomization analyses suggested that serum calcium levels were inversely associated with overall OA (95% CI, 0.595, 0.850), hip OA (95% CI, 0.352, 0.799) and knee OA (95% CI, 0.461, 0.901). Serum retinol levels were also inversely associated with hip OA (95% CI, 0.257, 0.778). Moreover, sex-specific associations were observed between serum calcium levels (95% CI, 0.936, 0.998), iron levels (95% CI, 1.000, 1.012), selenium levels (95% CI, 0.923, 0.999) and OA in women. CONCLUSION: In this study, an inverse causal association between serum calcium levels and OA was established. Serum retinol levels were inversely associated with hip OA. In addition, we provide evidence for the causal effect of serum calcium, iron and selenium on the risk of OA in women.


Subject(s)
Calcium/blood , Iron/blood , Osteoarthritis/blood , Selenium/blood , Vitamin A/blood , Female , Humans , Magnetic Resonance Spectroscopy , Male , Mendelian Randomization Analysis , Nutritional Status , Sex Factors
7.
Calcif Tissue Int ; 108(3): 281-287, 2021 03.
Article in English | MEDLINE | ID: mdl-33068140

ABSTRACT

Previous observational studies have identified various risk factors associated with the development of osteoporosis, including sex hormone-binding globulin (SHBG). The aim of this study was to determine the potential causal effects of circulating SHBG concentrations on bone mineral density (BMD). Two-sample Mendelian randomization (MR) approach was applied in analyses. From summary-level data of genome-wide association studies (GWAS), we selected 11 single-nucleotide polymorphisms (SNPs) associated with SHBG levels as instrumental variable, and used summary statistics for BMD at forearm (FA) (n = 8143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498) and heel (HL) (n = 394,929), and total-body BMD of different age-stages (15 or less, 15-30, 30-45, 45-60, 60 or more years old) (n = 67,358). Inverse causal associations was observed between SHBG levels and FA BMD (Effect = - 0.26; 95% CI - 0.49 to - 0.04; P = 0.022), HL eBMD (Effect = - 0.09; 95% CI - 0.12 to - 0.06; P = 3.19 × 10-9), and total-body BMD in people aged 45-60 years (Effect = - 0.16; 95% CI - 0.31 to - 2.4 × 10-3; P = 0.047) and over 60 years (Effect = - 0.19; 95% CI - 0.33 to - 0.05; P = 0.006). Our study demonstrates that circulating SHBG concentrations are inversely associated with FA and HL eBMD, and total-body BMD in people aged over 45 years, suggesting that the role of SHBG in the development of osteoporosis might be affected by chronological age of patients and skeletal sites.


Subject(s)
Bone Density , Sex Hormone-Binding Globulin , Adolescent , Adult , Femur Neck , Genome-Wide Association Study , Humans , Mendelian Randomization Analysis , Middle Aged , Osteoporosis/genetics , Polymorphism, Single Nucleotide , Sex Hormone-Binding Globulin/analysis , Young Adult
8.
J Clin Pharm Ther ; 46(5): 1441-1458, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34254696

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: The benefits of local infiltration analgesia (LIA) in knee arthroplasty (KA) have been well-documented. However, it is unknown whether adding a corticosteroid to the composition of the LIA is beneficial. This study aimed to investigate the efficacy and safety of administering periarticular steroids intraoperatively in patients who underwent KA through a systematic review and meta-analysis. METHODS: A systematic search was conducted to identify relevant randomized controlled trials in the PubMed, Embase, Web of Science and Cochrane databases up to January 19th, 2021 to perform a meta-analysis. Outcome variables included pain scores, total opioid consumption, knee range of motion (ROM) and postoperative complications. RESULTS: Corticosteroid injections did not reduce pain scores at 6, 12, 24 or 72 h postoperatively, although a minimal degree of transient pain relief was achieved at 48 h postoperatively compared with those in the placebo group, nor was there a significant difference in total opioid consumption. However, patients receiving corticosteroids did exhibit a transient ROM increase on postoperative days 1, 2 and 3. Since the minimal clinically important difference (MCID) for ROM is unclear, it is unknown if the improvement in ROM is clinically significant. WHAT IS NEW AND CONCLUSION: Our specific end-point analysis demonstrated that corticosteroid administration did not provide pain relief or reduce opioid consumption compared with placebo. However, corticosteroids might provide a statistically significant, though transient and minimal improvement in knee ROM after KA, although no firm conclusions about the benefits of administering corticosteroids in KA can be made based on the available evidence.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anesthetics, Local/therapeutic use , Arthroplasty, Replacement, Knee/methods , Pain, Postoperative/drug therapy , Adrenal Cortex Hormones/administration & dosage , Analgesics, Opioid/administration & dosage , Anesthetics, Local/administration & dosage , Humans , Injections, Intra-Articular , Pain Management/methods , Postoperative Complications/epidemiology , Randomized Controlled Trials as Topic , Range of Motion, Articular
9.
J Cell Mol Med ; 24(1): 930-940, 2020 01.
Article in English | MEDLINE | ID: mdl-31701670

ABSTRACT

NR4A3 is a member of nuclear receptor subfamily 4, which is an important regulator of cellular function and inflammation. In this study, high expression of NR4A3 in human osteoarthritis (OA) cartilage was firstly observed. To explore the relationship between NR4A3 and OA, we used a lentivirus overexpression system to simulate its high expression and study its role in OA. Additionally, siRNA-mediated knockdown of NR4A3 was used to confirm the findings of overexpression experiments. The results showed the stimulatory effect of IL-1ß on cartilage matrix-degrading enzyme expression such as MMP-3, 9, INOS and COX-2 was enhanced in NR4A3-overexpressed chondrocytes and decreased in NR4A3-knockdown chondrocytes at both mRNA and protein levels, while IL-1ß-induced chondrocyte-specific gene (collagen 2 and SOX-9) degradation was only regulated by NR4A3 at protein level. Furthermore, overexpression of NR4A3 would also enhance EBSS-induced chondrocytes apoptosis, while knockdown of NR4A3 decreased apoptotic level after EBSS treatment. A pathway study indicated that IL-1ß-induced NF-κB activation was enhanced by NR4A3 overexpression and reduced by NR4A3 knockdown. We suggest that NR4A3 plays a pro-inflammatory role in the development of OA, and we also speculate that NR4A3 mainly regulates cartilage matrix-degrading gene expression under inflammatory conditions via the NF-κB pathway.


Subject(s)
Chondrocytes/pathology , DNA-Binding Proteins/metabolism , Gene Expression Regulation , Inflammation/pathology , Osteoarthritis/pathology , Receptors, Steroid/metabolism , Receptors, Thyroid Hormone/metabolism , Animals , Apoptosis , Case-Control Studies , Cells, Cultured , Chondrocytes/metabolism , DNA-Binding Proteins/genetics , Female , Humans , Inflammation/genetics , Inflammation/metabolism , Male , Osteoarthritis/genetics , Osteoarthritis/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Steroid/genetics , Receptors, Thyroid Hormone/genetics , Signal Transduction
10.
FASEB J ; 33(2): 2574-2586, 2019 02.
Article in English | MEDLINE | ID: mdl-30285579

ABSTRACT

Postmenopausal osteoporosis is initiated by estrogen withdrawal and is characterized mainly by overactivated osteoclastic bone resorption. Targeting TNF receptor-associated factor 6 (TRAF6) or its downstream signaling pathways to modulate osteoclast formation and function is an appealing strategy for osteoclast-related disorders. In the present study, we determined the effect of tomatidine, a steroidal alkaloid derived from Solanaceae, on the formation and function of receptor activator of NF-κB (RANK) ligand-induced osteoclasts and the underlying mechanism. Tomatidine inhibited osteoclast formation in a dose-dependent manner and decreased the expression of osteoclast marker genes. Actin ring formation and osteoclastic bone resorption were attenuated in the presence of tomatidine in vitro. Eight weeks after ovariectomy, tomatidine prevented estrogen deficiency-induced bone loss and restored the mechanical properties of the femur. At the molecular level, tomatidine abrogated phosphorylation of c-Jun N-terminal kinase (JNK)/p38, NF-κB, and protein kinase B (Akt) pathway proteins by suppressing RANK expression, inhibiting the binding of TRAF6 to RANK, and downregulating the osteoclastogenesis marker-related protein expression. In summary, these data demonstrated that tomatidine attenuated osteoclast formation and function by modulating multiple TRAF6-mediated pathways. Therefore, tomatidine could be a novel candidate for the treatment of osteoclast-related disorders, including osteoporosis.-Hu, B., Sun, X., Yang, Y., Ying, Z., Meng, J., Zhou, C., Jiang, G., Li, S., Wu, F., Zhao, X., Zhu, H., Wu, H., Cai, X., Shi, Z., Yan, S. Tomatidine suppresses osteoclastogenesis and mitigates estrogen deficiency-induced bone mass loss by modulating TRAF6-mediated signaling.


Subject(s)
Bone Resorption/drug therapy , Estrogens/toxicity , Gene Expression Regulation/drug effects , Osteoclasts/drug effects , Osteogenesis/drug effects , TNF Receptor-Associated Factor 6/metabolism , Tomatine/analogs & derivatives , Animals , Bone Resorption/etiology , Bone Resorption/metabolism , Bone Resorption/pathology , Cell Differentiation , Cells, Cultured , Female , Humans , Mice, Inbred C57BL , NF-kappa B/genetics , NF-kappa B/metabolism , Osteoclasts/cytology , Osteoclasts/metabolism , Ovariectomy/adverse effects , Signal Transduction , TNF Receptor-Associated Factor 6/genetics , Tomatine/pharmacology
11.
BMC Musculoskelet Disord ; 21(1): 48, 2020 Jan 22.
Article in English | MEDLINE | ID: mdl-31969161

ABSTRACT

BACKGROUND: Malignant fibrous neoplasms (MFN) of long bones are rare lesions. Moreover, the prognostic determinants of MFN of long bones have not been reported. This study aimed to present epidemiological data and analyse the prognostic factors for survival in patients with MFN. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) programme database was used to screen patients with malignant fibrous neoplasms (MFN) of long bones from 1973 to 2015, with attention to fibrosarcoma, fibromyxosarcoma, periosteal fibrosarcoma and malignant fibrous histiocytoma. The prognostic values of overall survival (OS) and cancer-specific survival (CSS) were assessed using the Cox proportional hazards regression model with univariate and multivariate analyses. The Kaplan-Meier method was used to obtain OS and CSS curves. RESULTS: A total of 237 cases were selected from the SEER database. Malignant fibrous histiocytoma was the most common form of lesion in long bones. Multivariate analysis revealed that independent predictors of OS included age, stage, tumour size and surgery. Age, stage, tumour size and surgery were also independent predictors of CSS. Additionally, the most significant prognostic factor was whether metastasis had occurred at the time of initial diagnosis. CONCLUSION: Among patients with MFN of long bones, age (> 60 years), tumour size (> 10 cm), distant stage, and non-surgical treatment are factors for poor survival.


Subject(s)
Bone Neoplasms/epidemiology , Databases, Factual/trends , Fibrosarcoma/epidemiology , Histiocytoma, Benign Fibrous/epidemiology , Population Surveillance , SEER Program , Adolescent , Adult , Bone Neoplasms/diagnosis , Female , Fibrosarcoma/diagnosis , Histiocytoma, Benign Fibrous/diagnosis , Humans , Male , Middle Aged , Neoplasm Staging/methods , Neoplasm Staging/trends , Population Surveillance/methods , Survival Rate/trends , Young Adult
12.
J Cell Mol Med ; 23(8): 5762-5770, 2019 08.
Article in English | MEDLINE | ID: mdl-31225720

ABSTRACT

Osteolysis is characterized by overactivated osteoclast formation and potent bone resorption. It is enhanced in many osteoclast-related diseases including osteoporosis and periprosthetic osteolysis. The shortage of effective treatments for these pathological processes emphasizes the importance of screening and identifying potential regimens that could attenuate the formation and function of osteoclasts. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone containing anti-inflammatory properties. Here, we showed that DHE suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and osteoclast marker gene expression. It also inhibited F-actin ring formation and bone resorption in a dose-dependent manner in vitro. Moreover, DHE inhibited the RANKL-induced phosphorylation of NF-κB, mitigated bone erosion in vivo in lipopolysaccharide-induced inflammatory bone loss model and particle-induced calvarial osteolysis model. Together, these results suggest that DHE reduces osteoclast-related bone loss via the modulation of NF-κB activation during osteoclastogenesis indicating that it might be a useful treatment for osteoclast-related skeletal disorders.


Subject(s)
Bone Resorption/pathology , Lactones/pharmacology , NF-kappa B/metabolism , Osteoclasts/pathology , Osteogenesis/drug effects , Sesquiterpenes/pharmacology , Signal Transduction , Actins/metabolism , Animals , Biomarkers/metabolism , Cell Differentiation/drug effects , Gene Expression Regulation/drug effects , Lactones/chemistry , Lipopolysaccharides , Macrophages/drug effects , Macrophages/metabolism , Male , Mice, Inbred C57BL , NFATC Transcription Factors/metabolism , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteolysis/pathology , RANK Ligand/pharmacology , Sesquiterpenes/chemistry , Signal Transduction/drug effects , Skull/drug effects , Skull/pathology
13.
J Cell Mol Med ; 23(10): 6730-6743, 2019 10.
Article in English | MEDLINE | ID: mdl-31328430

ABSTRACT

Osteoclast overactivation-induced imbalance in bone remodelling leads to pathological bone destruction, which is a characteristic of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, periprosthetic osteolysis and periodontitis. Natural compounds that suppress osteoclast formation and function have therapeutic potential for treating these diseases. Stachydrine (STA) is a bioactive alkaloid isolated from Leonurus heterophyllus Sweet and possesses antioxidant, anti-inflammatory, anticancer and cardioprotective properties. However, its effects on osteoclast formation and function have been rarely described. In the present study, we found that STA suppressed receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption, and reduced osteoclast-related gene expression in vitro. Mechanistically, STA inhibited RANKL-induced activation of NF-κB and Akt signalling, thus suppressing nuclear factor of activated T cells c1 induction and nuclear translocation. In addition, STA alleviated bone loss and reduced osteoclast number in a murine model of LPS-induced inflammatory bone loss. STA also inhibited the activities of NF-κB and NFATc1 in vivo. Together, these results suggest that STA effectively inhibits osteoclastogenesis both in vitro and in vivo and therefore is a potential option for treating osteoclast-related diseases.


Subject(s)
NF-kappa B/metabolism , Osteoclasts/drug effects , Osteogenesis/drug effects , Osteolysis/drug therapy , Proline/analogs & derivatives , Proto-Oncogene Proteins c-akt/metabolism , Actins/metabolism , Active Transport, Cell Nucleus/drug effects , Active Transport, Cell Nucleus/genetics , Animals , Cell Nucleus/metabolism , Cell Survival/drug effects , Cells, Cultured , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Lipopolysaccharides/toxicity , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , NFATC Transcription Factors/metabolism , Osteoclasts/metabolism , Osteogenesis/genetics , Osteolysis/chemically induced , Osteolysis/diagnostic imaging , Osteolysis/metabolism , Proline/pharmacology , Proline/therapeutic use , RANK Ligand/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , T-Lymphocytes/metabolism , Tomography, X-Ray Computed
14.
Med Sci Monit ; 25: 6436-6445, 2019 Aug 27.
Article in English | MEDLINE | ID: mdl-31454342

ABSTRACT

BACKGROUND The aim of this study was to review the efficacy and safety of intra-articular (IA) viscosupplementation (VS) for hip osteoarthritis (OA). MATERIAL AND METHODS We searched Medline, Clinical Trial Register Center, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing VS with placebo injection for hip OA. We included suitable studies, assessed the quality of studies, and extracted data on pain reduction, function improvement at different time points, and safety profiles. The comparisons of pain and function outcome were performed by meta-analysis. RESULTS Five high-quality randomized controlled studies trials (RCTs) with 591 patients with hip OA were identified. Although several trials demonstrated a significant decline in pain in VS groups during follow-up compared to baseline, without severe adverse events, the pooled analysis did not show VS was superior to placebo at any time windows [7-14 days: standardized mean difference (SMD): -0.18; 95% CI, -0.47 to 0.10, p=0.21; 28-30 days: 0.02 (-0.15, 0.19), p=0.82; or at final visit: -0.14 (-0.46, 0.18), p=0.38]. Similar results were also observed in the combined data of functional results. CONCLUSIONS IA VS does not reduce pain or improve function significantly better than placebo in a short-term follow-up. The benefits and safety of VS should be further assessed by sufficiently-sized, methodologically sound studies with validated assessment of more clinically relevant end-points.


Subject(s)
Osteoarthritis, Hip/drug therapy , Viscosupplementation , Clinical Trials as Topic , Humans , Injections, Intra-Articular/adverse effects , Pain/drug therapy , Quality Assurance, Health Care , Treatment Outcome , Viscosupplementation/adverse effects
15.
Med Sci Monit ; 25: 5525-5535, 2019 Jul 25.
Article in English | MEDLINE | ID: mdl-31344019

ABSTRACT

BACKGROUND Osseous malignant vascular tumors (OMVTs) are rare lesions. Moreover, the prognostic determinants of OMVTs have not been reported. This study aimed to present epidemiological data and analyze the prognostic factors of survival in OMVT patients. MATERIAL AND METHODS OMVT patients who were diagnosed between 1973 and 2015 were screened using the Surveillance, Epidemiology, and End Results (SEER) program database, with special attention paid to osseous hemangiosarcoma (OAS) and osseous hemangioendothelioma (OHE). We assessed the prognostic values of cancer-specific survival (CSS) and overall survival (OS) rates with a Cox proportional hazards regression model and univariate and multivariate analyses. OS and CSS curves were obtained using the Kaplan-Meier method. RESULTS A total of 202 cases were selected from the SEER database. The specific histopathological diagnoses were osseous hemangiosarcoma (n=127) and osseous hemangioendothelioma (n=75). Among OMVT patients, histology was an important factor in determining survival. Using multivariate analysis, old age, distant tumor stage, surgery, and low tumor grade were predictors of OS for OAS patients. Old age, surgery, and low tumor grade were predictors of CSS. Using multivariate analysis, old age and surgery were predictors of OS and CSS for OHE patients. CONCLUSIONS This study is the largest population-based study to show the demographic characteristics and analyze the prognosis of OMVT patients. Independent predictors of OS for patients with AS included old age, distant tumor stage, low tumor grade, and surgery. Old age, surgery, and low tumor grade were also predictors of CSS for patients with OAS. Independent predictors of CSS and OS for patients with OHE included old age and surgery.


Subject(s)
Bone Neoplasms/mortality , Vascular Neoplasms/mortality , Adult , Aged , Bone Neoplasms/epidemiology , Bone and Bones/metabolism , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Proportional Hazards Models , SEER Program , Survival Analysis , Survival Rate , Vascular Neoplasms/epidemiology
16.
J Shoulder Elbow Surg ; 28(5): 869-874, 2019 May.
Article in English | MEDLINE | ID: mdl-30509611

ABSTRACT

BACKGROUND: Anatomic skeletal features of the shoulder play important roles in anterior shoulder dislocation. However, studies on the effect of the humeral structure are few. This case-control study aimed to analyze the risk factors of anterior shoulder instability, including glenoid and humeral factors. METHODS: Anterior shoulder instability was found in 64 of 10,035 individuals who underwent magnetic resonance imaging. Propensity score matching was used to select controls matched for age, sex, height, and weight. We analyzed the glenoid and humeral structural data using conditional logistic regression analysis and identified cutoff points using receiver operating characteristic curve analysis. RESULTS: Significant differences were found between the control and dislocation groups in the depth-to-width ratio (0.119 ± 0.034 vs. 0.105 ± 0.037, P = .021), height-to-width ratio (1.51 ± 0.13 vs. 1.67 ± 0.16, P < .001), humeral head diameter-to-glenoid fossa diameter ratio (1.56 ± 0.11 vs. 1.64 ± 0.20, P < .001), and humeral containing angle (67.3° ± 5.9° vs. 60.4° ± 5.9°, P < .001). The humeral containing angle (odds ratio, 0.95; P = .024) and the glenoid height-to-width ratio (odds ratio, 7.88; P = .002), adjusted for the depth-to-width ratio and diameter ratio, were associated with anterior shoulder instability. The cutoff point for the humeral containing angle was 64° and for the height-to-width ratio was 1.60. CONCLUSIONS: This study revealed significant risk factors for shoulder instability in the Chinese Han population. The humeral containing angle and the glenoid height-to-width ratio were risk factors for anterior shoulder instability.


Subject(s)
Joint Instability/etiology , Shoulder Dislocation/etiology , Adult , Case-Control Studies , Female , Glenoid Cavity/pathology , Humans , Humeral Head/pathology , Joint Instability/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Odds Ratio , Risk Factors , Scapula/pathology , Shoulder Dislocation/diagnostic imaging , Young Adult
17.
J Cell Mol Med ; 22(10): 5121-5131, 2018 10.
Article in English | MEDLINE | ID: mdl-30063119

ABSTRACT

Metabolism of bone is regulated by the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Activation of osteoclasts could lead to osteoporosis. Thus, inhibiting the activity of osteoclasts becomes an available strategy for the treatment of osteoporosis. Tectorigenin is an extract of Belamcanda chinensis In the present study, the anti-osteoclastogenesis effects of tectorigenin were investigated in vitro and in vivo. The results showed preventive and therapeutic effects of tectorigenin at concentrations of 0, 10, 40, and 80 µmol/L in the maturation and activation of osteoclasts. A signalling study also indicated that tectorigenin treatment reduces activation of NF-κB signalling in osteoclastogenesis. Animal experiment demonstrated that tectorigenin treatment (1-10 mg/kg, abdominal injection every 3 days) significantly inhibits bone loss in ovariectomized C57BL/6. Our data suggest that tectorigenin is a potential pharmacological choice for osteoporosis.


Subject(s)
Bone Resorption/drug therapy , Isoflavones/administration & dosage , Osteogenesis/drug effects , Osteoporosis/drug therapy , Animals , Bone Resorption/genetics , Bone Resorption/pathology , Cell Differentiation/drug effects , Disease Models, Animal , Humans , Mice , NF-kappa B/genetics , Osteoblasts/drug effects , Osteoclasts/drug effects , Osteogenesis/genetics , Osteoporosis/genetics , Osteoporosis/pathology , Ovariectomy/adverse effects , RANK Ligand/genetics , Signal Transduction/drug effects , Transcription Factor RelA/genetics
18.
Int J Med Sci ; 15(13): 1458-1465, 2018.
Article in English | MEDLINE | ID: mdl-30443165

ABSTRACT

Aseptic loosening is the most common complication of joint replacement. Previous studies showed that acrylic bone cement loaded with a commercially-available alendronate powder (APAC) had good promise against wear debris-mediated osteolysis for prevention of aseptic loosening. The purpose of the present study was to investigate the effect of adding alendronate powder to an acrylic bone cement on quasi-static mechanical properties (namely, compressive strength, compressive modulus, tensile strength, and flexural strength), fatigue life, porosity, and microstructure of the cement. The results showed that adding up to 1 wt./wt.% alendronate powder exerted no detrimental effect on any of the quasi-static mechanical properties. However, the fatigue life of APAC decreased by between ~17% and ~27 % and its porosity increased by between ~ 5-7 times compared with corresponding values for the control cement (no alendronate powder added). Fatigue life was negatively and significantly correlated with porosity. Considering that fatigue life of the cement plays a significant role in joint replacement survival, clinical use of APAC cannot be recommended.


Subject(s)
Alendronate/chemistry , Polymethyl Methacrylate/chemistry , Fatigue , Humans , Porosity
19.
Med Sci Monit ; 24: 797-802, 2018 Feb 08.
Article in English | MEDLINE | ID: mdl-29415980

ABSTRACT

BACKGROUND Calcium phosphate cement (CPC) has been applied as a biodegradable antibiotic carrier in osteomyelitis. However, the drug delivery, antibacterial efficacy, and degradation rate of CPC are insufficient and require further improvement in clinical application. MATERIAL AND METHODS Vancomycin-loaded CPC columns were prepared, and eluted in simulated body fluid. The drug delivery was assessed in the ultrasound group and control group by fluorescence polarization immunoassay. The antibacterial efficacy of vancomycin in the ultrasound group and control groups was investigated by standard plate count method. Low-frequency pulsed ultrasound (46.5 kHz, 900 mW/cm²) was used to produce a sinusoidal wave in the ultrasound groups. The percentage of residual weight was evaluated to assess the degradation of CPC. RESULTS The concentration and cumulatively released percentage of vancomycin in the ultrasound group were higher than that in the control group at each time point (p<0.05). The duration of vancomycin concentration over the level of minimum inhibitory concentration was significantly prolonged in the ultrasound group (p<0.05). Antibacterial efficacy of vancomycin in the ultrasound group was significantly greater than that in the control group with same concentration of vancomycin (p<0.05). The percentage of residual weight in the ultrasound group was significantly less than that in the control group (p<0.05). CONCLUSIONS Low-frequency pulsed ultrasound can enhance vancomycin release, prolong the duration of vancomycin concentration at high levels, and accelerate the degradation rate of vancomycin-loaded CPC.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bone Cements/pharmacology , Calcium Phosphates/pharmacology , Drug Delivery Systems , Ultrasonic Waves , Vancomycin/pharmacology , Drug Liberation , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects
20.
BMC Musculoskelet Disord ; 19(1): 19, 2018 01 17.
Article in English | MEDLINE | ID: mdl-29343245

ABSTRACT

BACKGROUND: Although thrombosis complication is rare after arthroscopic meniscus surgery, deep vein thrombosis and pulmonary embolism can be fatal. The associated risk factors and whether anticoagulant prevention after arthroscopic knee surgery is necessary have not reach consensus. Here we present a case of deep vein thrombosis and pulmonary embolism after a common arthroscopic meniscectomy. CASE PRESENTATION: The patient had no risk factors except ipsilateral leg varicose veins. She present swell at knee and calf from postoperative 3 weeks, and developed dyspnea, palpitation, and nausea on 33th day, pulmonary embolism was confirmed with CT angiography at emergency department. After thrombolysis and anticoagulation therapy were administered, the patient improved well and discharged. And the intravenous ultrasound confirmed thrombosis of popliteal vein and small saphenous vein. Who don't have common risk factors for venous thromboembolism. CONCLUSIONS: Despite the low incidence of thromboembolic complications after simple arthroscopy surgery, its life-threatening and devastating property make clinicians rethink the necessity of thromboprophylaxis and importance of preoperative relative risk factors screening.


Subject(s)
Arthroscopy/adverse effects , Pulmonary Embolism/diagnostic imaging , Tibial Meniscus Injuries/diagnostic imaging , Tibial Meniscus Injuries/surgery , Venous Thrombosis/diagnostic imaging , Arthroscopy/trends , Female , Humans , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Pulmonary Embolism/etiology , Venous Thrombosis/etiology
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